Interaction of epidermal growth factor with the hypothalamic-pituitary-adrenal axis: potential physiologic relevance

Epidermal growth factor (EGF), a polypeptide mitogen that participates in wound healing, has ACTH-like activity in ewes. We examined its effects on the primate hypothalamic-pituitary-adrenal (HPA) axis by administering mouse EGF (mEGF) iv (0-100 micrograms/kg) to rhesus monkeys. mEGF caused dose-dependent elevations of plasma ACTH and cortisol in these animals. To define whether the locus of stimulation was the hypothalamus and/or the pituitary gland we examined the capacity of mEGF to directly stimulate hypothalamic CRH or pituitary ACTH secretion in a rat hypothalamic organ culture system and a rat pituitary cell system, respectively. mEGF stimulated hypothalamic CRH release in a dose-dependent manner, but failed to cause pituitary ACTH release. We conclude that EGF is a stimulator of the HPA axis in primates. Thus, EGF, and/or one of its naturally occurring analogs, may participate in the physiological activation of the HPA axis at times during which the concentrations of these factors are raised in the systemic circulation and/or locally in the hypothalamus. Such states may include trauma, surgery, and possibly emotional stress.